AzTrials
AzTrials

Multiple MyelomaPhase 3NCT02181413

A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant

A Phase 3 study testing Ixazomib Citrate in people with Multiple Myeloma and Autologous Stem Cell Transplant, run by Takeda at 227 sites in 33 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to determine the effect of ixazomib citrate maintenance therapy on progression-free survival (PFS), compared to placebo, in participants with newly diagnosed multiple myeloma (NDMM) who have had a response (complete response [CR], very good partial response [VGPR], or partial response… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ixazomib Citrate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
656 participants
Where
227 sitesin 33 countries
Study dates
16 Jul 2014to 8 Sep 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic multiple myeloma according to standard criteria.
  • Documented results of cytogenetics/ fluorescence in situ hybridization (FISH) obtained at any time before transplant, and International Staging System (ISS) staging at the time of diagnosis available.
  • Underwent standard of care (SOC) induction therapy (induction therapy must include proteasome inhibitor (PI) and/or immunomodulating drugs (IMiD)-based regimens as primary therapy for multiple myeloma), followed by a single autologous stem cell transplant (ASCT) with a high-dose melphalan (200 mg/m^2) conditioning regimen, within 12 months of diagnosis. Vincristine, Adriamycin [doxorubicin], and dexamethasone (VAD) is not an acceptable induction therapy for this trial.
  • Started screening no earlier than 75 days after transplant, completed screening within 15 days, and randomized no later than 115 days after transplant.
  • Must have not received post-ASCT consolidation therapy.
  • Documented response to ASCT (PR, VGPR, CR/stringent complete response [sCR]) according to IMWG criteria.
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  • ECOG performance status of 0 to 2.
  • Female participants who:
  • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, AND
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.) Male participants, even if surgically sterilized (ie, status postvasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, AND
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
  • Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
  • Suitable venous access for the study-required blood sampling.
  • Is willing and able to adhere to the study visit schedule and other protocol requirements.
  • Must meet the following clinical laboratory criteria at study entry:
  • Absolute neutrophil count (ANC) ≥ 1,000 per cubic milliliter (/mm^3) and platelet count ≥ 75,000/mm^3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days before randomization.
  • Total bilirubin ≤ 1.5 * the upper limit of the normal range (ULN).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 * ULN.
  • Calculated creatinine clearance ≥ 30 milliliter per minute (mL/min).

Who cannot join

  • Multiple myeloma that has relapsed following primary therapy or is not responsive to primary therapy. For this study, stable disease following ASCT will be considered nonresponsive to primary therapy.
  • Double (tandem) ASCT.
  • Radiotherapy within 14 days before the first dose of study drug.
  • Diagnosed or treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy with evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
  • Major surgery within 14 days before randomization.
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  • Central nervous system involvement.
  • Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before randomization.
  • Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
  • Systemic treatment with strong cytochrome P450 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before randomization in the study.
  • Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
  • Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause).
  • Psychiatric illness/social situation that would limit compliance with study requirements.
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  • Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
  • Treatment with any investigational products within 60 days before the first dose of the study drug regimen.

Trial locations and contacts

227 sites in 33 countries.

227 sites in 33 countries

Germany23 sites

  • Helios Klinikum Berlin-Buch

    Berlin, 13125

  • Charite - Universitatsmedizin Berlin

    Berlin, 13353

  • Universitatsklinikum Bonn

    Bonn, North Rhine-Westphalia, 53105

  • Uniklinik Koln

    Cologne, North Rhine-Westphalia, 50937

  • Klinikum Darmstadt GmbH

    Darmstadt, Hesse, 64283

  • Universitatsklinikum Carl Gustav Carus an der TU Dresden

    Dresden, Saxony, 1307

  • Universitatsklinikum Essen

    Essen, North Rhine-Westphalia, 45122

  • Evangelisches Krankenhaus Essen Werden gGmbH

    Essen, North Rhine-Westphalia, 45239

  • Klinikum Frankfurt Hochst GmbH

    Frankfurt am Main, Hesse, 65929

  • Katholisches Krankenhaus Hagen gGmbH

    Hagen, North Rhine-Westphalia, 58095

  • Asklepios Klinik St. Georg

    Hamburg, 20099

  • Universitatsklinikum Hamburg Eppendorf

    Hamburg, 20246

  • Asklepios Klinik Altona

    Hamburg, 22763

  • KRH Klinikum Siloah-Oststadt-Heidehaus

    Hanover, 30459

  • University Clinic Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

  • Klinikum der Stadt Ludwigshafen gGmbH

    Ludwigshafen, 67063

  • Universitatsmedizin der Johannes Gutenberg-Universitat Mainz

    Mainz, Rhineland-Palatinate, 55131

  • Klinikum Mannheim Universitatsklinikum gGmbH

    Mannheim, Baden-Wurttemberg, 68167

  • LMU Klinikum der Universitat Munchen

    München, Bavaria, 81377

  • Pius Hospital Oldenburg

    Oldenburg, Lower Saxony, 26121

  • Universitatsklinikum Tubingen

    Tübingen, 72076

  • Universitatsklinikum Ulm

    Ulm, Baden-Wurttemberg, 89081

  • Universitatsklinikum Wurzburg

    Würzburg, Bavaria, 97080

Other trials in Germany

Japan17 sites

  • Juntendo University Hospital

    Bunkyo, Tokyo, 113-8431

  • Chiba University Hospital

    Chiba, Tokyo, 2608677

  • Kyushu University Hospital

    Fukuoka, 812-8582

  • Saitama Medical Center

    Kawagoe, Saitama, 350-8550

  • Kobe City Medical Center General Hospital

    Kobe, Hyōgo, 650-0047

  • Iwate Medical University Hospital

    Morioka, Iwate, 020-8505

  • National Hospital Organization Nagoya Medical Center

    Nagoya, 460-0001

  • Nagoya City University Hospital

    Nagoya, 467-8602

  • Niigata Cancer Center Hospital

    Niigata, Niigata, 951-8566

  • National Hospital Organization Okayama Medical Center

    Okayama, Okayama-ken, 701-1192

  • National Hospital Organization Sendai Medical Center

    Sendai, Miyagi, 9838520

  • National Hospital Organaization Shibukawa Medical Center

    Shibukawa, 377-0280

  • Japanese Red Cross Medical Center

    Shibuya-ku, Tokyo, 150-8935

  • Center Hospital of the National Center for Global Health and Medicine

    Shinjuku, Tokyo, 162-8655

  • Keio University Hospital

    Shinjuku-ku, Tokyo, 160-8582

  • National Hospital Organization Disaster Medical Center

    Tachikawa, 1900014

  • Toyohashi Municipal Hospital

    Toyohashi, 441-8570

Other trials in Japan

Brazil15 sites

  • Hospital Das Clinicas Da Universidade Federal de Minas Gerais

    Belo Horizonte, Minas Gerais, 30130-100

  • Instituto de Oncologia Do Parana

    Curitiba, Paraná, 80530-010

  • Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner

    Curitiba, Paraná, 81520-060

  • Centro de Pesquisas Oncologicas

    Florianópolis, Santa Catarina, 88034000

  • Hospital Amaral Carvalho

    Jaú, São Paulo, 17210-080

  • Instituto Joinvilense de Hematologia E Oncologia

    Joinville, Santa Catarina, 89201-260

  • Hospital de Clinicas de Passo Fundo

    Passo Fundo, Rio Grande do Sul, 99010-260

  • Hospital de Clinicas de Porto Alegre (HCPA) - PPDS

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Mae de Deus Center Hospital Giovanni Battista

    Porto Alegre, Rio Grande do Sul, 90470-340

  • Instituto Nacional de Cancer

    Rio de Janeiro, 20231-050

  • Universidade Federal do Rio de Janeiro - UFRJ

    Rio de Janeiro, 21941-913

  • Hospital de Base Da FAMERP

    São José do Rio Preto, São Paulo, 15090-000

  • Irmandade Da Santa Casa de Misericordia de Sao Paulo

    São Paulo, 01223-001

  • Hospital Israelita Albert Einstein

    São Paulo, 05651-901

  • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

    São Paulo, 5403000

Other trials in Brazil

Israel14 sites

  • Barzilai Medical Center

    Ashkelon, 78278

  • Soroka University Medical Centre

    Beersheba, 84101

  • Bnai Zion Medical Center

    Haifa, 31048

  • Rambam Medical Center - PPDS

    Haifa, 31096

  • Lady Davis Carmel Medical Center

    Haifa, 34362

  • Shaare Zedek Medical Center

    Jerusalem, 91031

  • Hadassah Medical Center PPDS -

    Jerusalem, 91120

  • Galilee Medical Center

    Nahariya, 22100

  • Rabin Medical Center - PPDS

    Petah Tikva, 49100

  • Sheba Medical Center - PPDS

    Ramat Gan, 52621

  • Kaplan Medical Center

    Rehovot, 76100

  • ZIV Medical Center

    Safed, 13100

  • Tel Aviv Sourasky Medical Center PPDS

    Tel Aviv, 64239

  • Shamir Medical Center Assaf Harofeh

    Tzrifin, 70300

Other trials in Israel

Italy14 sites

  • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi

    Ancona, The Marches, 60020

  • Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi

    Bologna, 40138

  • ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN

    Brescia, 25123

  • Azienda Ospedaliera Universitaria Careggi

    Florence, 50134

  • IRCCS Az. Osp. Universitaria San Martino- IST

    Genova, 16132

  • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l - PPDS

    Meldola, 47014

  • ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda

    Milan, 20162

  • Fondazione IRCCS Policlinico San Matteo di Pavia

    Pavia, Lombardy, 27100

  • Presidio Ospedaliero di Pescara

    Pescara, Abruzzo, 65100

  • Ospedale Infermi di Rimini

    Rimini, 47900

  • IRCCS Centro Di Riferimento Oncologico Della Basilicata

    Rionero in Vulture, Potenza, 85028

  • Azienda Ospedaliera San Camillo Forlanini

    Rome, Lazio, 152

  • Azienda Ospedaliera S Maria Di Terni

    Terni, Umbria, 5100

  • Azienda Ospedaliera Citta della Salute e della Scienza di Torino

    Turin, Piedmont, 10126

Other trials in Italy

Spain13 sites

  • Hospital Universitario Germans Trias i Pujol

    Badalona, Barcelona, 8916

  • Hospital Clinic de Barcelona

    Barcelona, 8036

  • C.H. Regional Reina Sofia - PPDS

    Córdoba, 14004

  • Institut Catala d'Oncologia Girona

    Girona, 17007

  • Hospital General Universitario Gregorio Maranon

    Madrid, Madrid, Communidad Delaware, 28009

  • Hospital Universitario de La Princesa

    Madrid, 28006

  • Hospital Universitario La Paz - PPDS

    Madrid, 28046

  • Hospital Universitario HM Sanchinarro CIOCC

    Madrid, 28050

  • Hospital Universitario Puerta de Hierro - Majadahonda

    Madrid, 28222

  • Hospital General Universitario Morales Meseguer

    Murcia, 30008

  • Clinica Universidad Navarra

    Pamplona, Navarre, 31008

  • Complejo Asistencial Universitario de Salamanca H. Clinico

    Salamanca, 37007

  • Hospital Universitario Virgen del Rocio - PPDS

    Seville, 41013

Other trials in Spain

United Kingdom11 sites

  • St James University Hospital

    Leeds, Yorkshire, LS9 7TF

  • University Hospitals Leicester

    Leicester, LE1 5WW

  • Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre

    London, London, City of, EC1A 7BE

  • Kings College Hospital

    London, London, City of, SE5 9RS

  • Imperial College Healthcare NHS Trust

    London, London, City of, W12 0HS

  • University College London Hospitals (UCLH)

    London, WC1E 6AG

  • Churchill Hospital

    Oxford, Oxfordshire, OX3 7LJ

  • Royal Hallamshire Hospital

    Sheffield, Yorkshire, S10 2JF

  • Southampton General Hospital

    Southampton, Hampshire, SO16 6YD

  • Royal Marsden Hospital - Surrey

    Sutton, Surrey, SM2 5PT

  • Singleton Hospital - PPDS

    Swansea

Other trials in United Kingdom

Australia9 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Austin Health

    Heidelberg, Victoria, 3084

  • St George Hospital

    Kogarah, New South Wales, 2217

  • The Alfred Hospital

    Melbourne, Victoria, 3004

  • Icon Cancer Care South Brisbane

    South Brisbane, Queensland, 4101

  • Gold Coast University Hospital

    Southport, Queensland, 4215

  • Calvary Mater Newcastle

    Waratah, New South Wales, 2298

  • Westmead Hospital

    Westmead, New South Wales, 2145

  • The Queen Elizabeth Hospital

    Woodville South, South Australia, 5011

Other trials in Australia

South Korea9 sites

  • Chungnam National University Hospital

    Daejeon, 301-721

  • National Cancer Center

    Goyang, Gyeonggido, 410769

  • Gachon University Gil Medical Center Pharmacy

    Incheon, 405-760

  • Seoul National University Hospital

    Seoul, 110744

  • Severance Hospital Yonsei University Health System - PPDS

    Seoul, 120-752

  • Samsung Medical Center - PPDS

    Seoul, 135-710

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul, 137-701

  • Asan Medical Center - PPDS

    Seoul, 138-736

  • Ewha Womans University Mokdong Hospital

    Seoul, 158710

Other trials in South Korea

Denmark7 sites

  • Aalborg Universitetshospital

    Aalborg, North Denmark, DK-9000

  • Aarhus Universitetshospital Arhus Sygehus

    Aarhus N, DK-8200

  • Rigshospitalet

    Copenhagen, 2100

  • Herlev Hospital

    Herlev, Capital, 2730

  • Odense Universitetshospital

    Odense, 5000

  • Sjallands Universitetshospital, Roskilde

    Roskilde, DK-4000

  • Vejle Sygehus

    Vejle, DK-7100

Other trials in Denmark

Turkey (Türkiye)7 sites

  • Hacettepe Universitesi Tip Fakultesi Hastanesi

    Ankara, 6100

  • Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi

    Ankara, 6200

  • Ankara University Medical Faculty PPDS

    Ankara

  • Pamukkale Universitesi Tip Fakultesi Hastanesi

    Denizli, 20070

  • Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi

    Istanbul, 34093

  • Erciyes Universitesi Tip Fakultesi Hastanesi

    Kayseri, 38039

  • Karadeniz Technical University Faculty of Medicine

    Trabzon, 61080

Other trials in Turkey (Türkiye)

United States6 sites

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • Penn State Health Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • West Virginia University Hospital

    Morgantown, West Virginia, 26506

  • Mayo Clinic - PPDS

    Rochester, Minnesota, 55905

  • Montefiore Medical Center

    The Bronx, New York, 10467

Other trials in United States

Argentina6 sites

  • Hospital Italiano de Buenos Aires

    Buenos Aires, C1181ACH

  • Hospital Italiano de La Plata

    La Plata, Buenos Aires, B1900AX

  • Instituto de Hematologia Y Medicina Clinica Dr Ruben Davoli

    Rosario, Santa Fe Province, 2000

  • Sanatorio Britanico de Rosario

    Rosario, Santa Fe Province, S2000CVB

  • Sanatorio Parque de Rosario

    Rosario, Santa Fe Province, S2000DSV

  • Hospital Iturraspe

    Santa Fe, S3006FTP

Other trials in Argentina

Belgium6 sites

  • ZNA Middelheim

    Antwerp, 2020

  • ZNA Stuivenberg

    Antwerp, 2060

  • AZ Sint-Jan AV

    Bruges, West-Vlaanderen, 8000

  • UZ Gent

    Ghent, Oost-Vlaanderen, 9000

  • Centre Hospitalier Jolimont-Lobbes

    La Louvière, Hainaut, 7100

  • Centre Hospitalier Universitaire Ambroise Pare

    Mons, Hainaut, 7000

Other trials in Belgium

Czechia6 sites

  • Fakultni nemocnice Brno

    Brno, 625 00

  • Fakultni nemocnice Hradec Kralove

    Hradec Králové, Kralovehradeck Kraj, 500 05

  • Fakultni nemocnice Olomouc

    Olomouc, 779 00

  • Fakultni nemocnice Ostrava

    Ostrava, 708 52

  • Fakultni nemocnice Kralovske Vinohrady

    Prague, 100 34

  • Vseobecna Fakultni Nemocnice V Praze

    Prague, 128 08

Other trials in Czechia

Poland6 sites

  • Szpital Specjalistyczny w Brzozowie

    Brzozów, 36-200

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

    Chorzów, Silesian Voivodeship, 41-500

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, Pomeranian Voivodeship, 80-952

  • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi

    Lodz, 93-510

  • Wojskowy Instytut Medyczny

    Warsaw, Masovian Voivodeship, 04-141

  • Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu

    Wroclaw, Lower Silesian Voivodeship, 50-367

Other trials in Poland

France5 sites

  • Hopital Antoine Beclere

    Clamart, Hauts-de-Seine, 92140

  • CHRU Lille

    Lille, Nord, 59037

  • Hopital Universitaire Dupuytren

    Limoges, 87042

  • Hotel Dieu - Nantes

    Nantes, Loire-Atlantique, 44093

  • Groupe Hospitalier Necker Enfants Malades

    Paris, 75015

Other trials in France

Hungary5 sites

  • Semmelweis Egyetem

    Budapest, 1083

  • Del-pesti Centrumkorhaz- Orszagos Hematologiai es Infektologiai Intezet

    Budapest, 1097

  • Debreceni Egyetem Klinikai Kozpont

    Debrecen, 4032

  • Somogy Megyei Kaposi Mor Oktato Korhaz

    Kaposvár, 7400

  • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

    Szeged, 6725

Other trials in Hungary

Netherlands5 sites

  • VU Medisch Centrum

    Amsterdam, North Holland, 1081 HV

  • Albert Schweitzer Ziekenhuis

    Dordrecht, South Holland, 3318 AT

  • Universitair Medisch Centrum Groningen

    Groningen, 9713 GZ

  • Erasmus MC

    Rotterdam, 3015 CE

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

Sweden5 sites

  • Sahlgrenska Universitetssjukhuset

    Gothenburg, Västra Götaland County

  • Helsingborg Lasarett

    Helsingborg, Skåne County

  • Skanes Universitetssjukhus Lund

    Lund, Skåne County

  • Karolinska Universitetssjukhuset Huddinge

    Stockholm, 14186

  • Akademiska Sjukhuset I Uppsala

    Uppsala, SE-751 85

Other trials in Sweden

Taiwan5 sites

  • Kaohsiung Medical University Hospital

    Kaohsiung City, 807

  • Chang Gung Medical Foundation-Kaoshiung Branch

    Kaohsiung City

  • National Taiwan University Hospital

    Taipei, 10002

  • Chang Gung Medical Foundation Chiayi Chang Gung Memorial Hospital

    Taipei, 613

  • Chang Gung Memorial Hospital, Linkou

    Taoyuan City, 333

Other trials in Taiwan

Austria4 sites

  • Elisabethinen Hospital Linz

    Linz, 4020

  • Salzburger Landeskliniken

    Salzburg, 5020

  • Allgemeines Krankenhaus der Stadt Wien

    Vienna, 1090

  • Klinik Ottakring (fruher: Wilhelminenspital)

    Vienna, 1160

Other trials in Austria

Greece4 sites

  • Evangelismos General Hospital of Athens

    Athens, Attica, 10676

  • Laiko General Hospital of Athens

    Athens, Attica, 11527

  • Alexandra Hospital

    Athens, 11528

  • Georgios Papanikolaou General Hospital of Thessaloniki

    Thessaloniki, 57010

Other trials in Greece

Norway4 sites

  • Vestre Viken HF Sykehuset Asker Og Barum

    Gjelta, Oppland, N-1346

  • Oslo Universitetssykehus HF, Ulleval

    Oslo, 450

  • Stavanger Universitetssykehus

    Stavanger, 4011

  • St. Olav's University Hospital

    Trondheim, Sor-Trondelag, N-7030

Other trials in Norway

Portugal4 sites

  • Hospital de Braga

    Braga, 4710-243

  • Centro Hospitalar E Universitario de Coimbra EPE

    Coimbra, 3000-075

  • Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS

    Porto, 4200-072

  • Centro Hospitalar de Sao Joao, E.P.E.

    Porto, 4200-319

Other trials in Portugal

Colombia3 sites

  • Instituto Nacional de Cancerologia Colombia

    Bogota, Cundinamarca

  • Fundacion Valle Del Lili

    Cali, Valle del Cauca Department

  • Hospital Pablo Tobon Uribe

    Medellín

Other trials in Colombia

South Africa3 sites

  • Medical Oncology Centre of Rosebank

    Johannesburg, Gauteng, 2196

  • Mary Potter Oncology Centre

    Pretoria, Gauteng, 181

  • Albert Alberts Stem Cell Transplant Centre

    Pretoria, Gauteng, 44

Other trials in South Africa

Canada2 sites

  • MUHC-Glen Site

    Montreal, Quebec, H4A 3J1

  • University Health Network

    Toronto, Ontario, M5G 2N2

Other trials in Canada

Mexico2 sites

  • Centro de Investigacion Farmaceutica Especializada de Occidente, SC - PPDS

    Guadalajara, Jalisco, 44160

  • Hospital Universitario Dr. Jose Eleuterio Gonzalez

    Monterrey, Nuevo León, 64460

Other trials in Mexico

Singapore2 sites

  • National University Hospital

    Singapore, 119074

  • Singapore General Hospital (SGH)

    Singapore, 169608

Other trials in Singapore

Switzerland2 sites

  • Universitatsspital Basel

    Basel, Basel-Stadt (de), 4031

  • Universitatsspital Zurich

    Zurich, Zurich (de), 8091

Other trials in Switzerland

Thailand2 sites

  • Chulalongkorn University

    Bangkok, Krung Thep Maha Nakhon-Bangkok, 10330

  • Phramongkutklao Hospital

    Bangkok, Krung Thep Maha Nakhon-Bangkok, 10400

Other trials in Thailand

Ukraine1 site

  • MNPE Kyiv Center of Bone Marrow Transplantation of executive body of Kyiv council

    Kyiv, 3115

Other trials in Ukraine

About this study

Official title: A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Patients With Multiple Myeloma Following Autologous Stem Cell Transplant

The purpose of this study is to determine the effect of ixazomib citrate maintenance therapy on progression-free survival (PFS), compared to placebo, in participants with newly diagnosed multiple myeloma (NDMM) who have had a response (complete response [CR], very good partial response [VGPR], or partial response [PR]) to induction therapy followed by high-dose therapy (HDT) and autologous stem cell transplant (ASCT).

Read the detailed description

The investigational drug being tested in this study is called ixazomib citrate. Ixazomib citrate is being tested to slow disease progression and improve overall survival in people who have NDMM and who have had any type of positive response to induction therapy followed by HDT and ASCT. This study will look at the effect ixazomib citrate has on the length of time that participants are free of progressive disease (PD) and their overall survival (OS).

The study enrolled 656 participants. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need, or if the disease has progressed and the information is required for planning the next treatment):

  • Ixazomib citrate 3 mg for the first 4 cycles, then 4 mg for the remaining 22 cycles
  • Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient.

All participants will be asked to take one capsule on Days 1, 8 and 15 of each 28-day cycle, for up to 26 cycles (approximately 24 months).

This multi-center trial will be conducted globally. The overall time to participate in this study is up to 107 months. Participants will make 28 visits to the clinic during the treatment period and will continue to make visits after treatment has ended. During this initial follow up period, participants will be assessed for disease status with follow up every 12 weeks. After the next line of therapy begins, follow-up will occur every 12 weeks until death or termination of the study.

Being tested
Ixazomib Citrate, Placebo
Keywords
Drug therapy, Ixazomib citrate
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ixazomib CitrateDrug

    Also called MLN9708

    Ixazomib citrate capsules

  • PlaceboDrug

    Ixazomib citrate placebo-matching capsules

Study groups in NCT02181413
Study groupRoleWhat they receive
PlaceboPlacebo comparatorIxazomib citrate placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 26 until PD, unacceptable toxicity, or discontinuation for alternate reasons.
Receives: Drug: Placebo
Ixazomib CitrateExperimentalIxazomib citrate 3 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib citrate 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 until PD, unacceptable toxicity, or discontinuation for alternate reasons. Participants who have had any dose reductions due to adverse events (AEs) would not be dose escalated.
Receives: Drug: Ixazomib Citrate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

    PFS was defined as the time from the date of randomization to the date of first documentation of PD, as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurred first. PD was defined as ≥25% increase from lowest value in: serum/urine M component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels must be >10 milligrams per deciliter (mg/dL); participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must have been ≥10%; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size increase; hypercalcemia development.

    Measured: Randomization up to End of treatment (EOT) (24 months); thereafter followed up every 4 weeks (up to 45 months)

Secondary outcomes (21)

  1. Overall Survival (OS)

    OS was measured as the time from the date of randomization to the date of death.

    Measured: Randomization up to end of follow up period (up to 107 months)

  2. Percentage of Participants With Any Best Response Category Before PD or Subsequent Therapy

    Response was assessed according to IMWG criteria. Best response includes partial response (PR), very good partial response (VGPR) and complete response (CR). PR as per IMWG criteria is 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to less than (<)200 milligrams (mg) per 24 hours. VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. CR is negative immunofixation of serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. Stringent CR (sCR) is CR and normal FLC ratio and absence of clonal plasma cells (PCs) by immunohistochemistry or 2- to 4-color flow cytometry. The decimal values of percentages were subjected to rounding off.

    Measured: Randomization up to EOT (up to 24 months) and thereafter every 4 weeks until initiation of the next line of therapy (up to 107 months)

  3. Time to Progression (TTP)

    TTP is defined as the time from the date of randomization to the date of first documentation of PD, using IMWG criteria. PD is defined as ≥25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be >10mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be ≥10%;new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development. Participants without documentation of PD at the time of analysis were censored at the date of last response assessment that is stable disease or better.

    Measured: Randomization up to PD (up to 107 months)

  4. Second Progression Free Survival (PFS2)

    PFS2 is defined as the time from the date of randomization to the date of objective disease progression on next line treatment or death from any cause (whichever occurs first). PD is defined as ≥25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be >10 mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be ≥10%; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development.

    Measured: Randomization up to EOT (24 months); thereafter followed up every 4 weeks until initiation of next-line therapy and then every 12 weeks until second progressive disease (PD2) or death (up to 107 months)

  5. Time to Start of the Next Line of Therapy

    Time to start of the next line of therapy was defined as the time from the date of randomization to the date of initiation dose of the next line of antineoplastic therapy following study treatment or death due to any cause, whichever occurred first. Participants who never took antineoplastic therapy were censored at the date of last contact or death.

    Measured: Randomization up to 107 months

  6. Time to End of the Next Line of Therapy

    Time to end of the next line of therapy was defined as the time from the date of randomization to the date of last dose of the next line of antineoplastic therapy following study treatment or death due to any cause, whichever occurred first or date of last contact for participants who never took antineoplastic therapy.

    Measured: Randomization up to 107 months

  7. Duration of the Next Line of Therapy

    Duration of the next line of therapy was defined as the time from the date of the first dose of the next line of therapy to the date of the last dose of the next antineoplastic therapy following study treatment or death due to any cause, whichever occurred first. Duration of the next line of therapy was analyzed on those participants who received the next line of therapy following the study treatment and duration was summarized using Kaplan-Meier method.

    Measured: Up to 107 months

  8. Percentage of Participants Who Develop a New Primary Malignancy

    The decimal values of percentages were subjected to rounding off.

    Measured: Up to 107 months

  9. Number of Participants With Conversion to Minimal Residual Disease (MRD) Negative

    MRD negativity (MRD-) is defined as absence of MRD and MRD positivity (MRD+) is defined as presence of MRD. The conversion rate from MRD positive to MRD negative was assessed and reported. Bone marrow aspirates and blood samples were sent to a central laboratory and were assessed for MRD using flow cytometry and a sequencing methodology.

    Measured: Baseline up to EOT (up to 24 months)

  10. Number of Participants With Maintenance of MRD Negativity

    MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. The maintenance of MRD negativity up to the end of treatment was assessed and reported in participants converting from MRD+ at Baseline to MRD negative. Bone marrow aspirates and blood samples were sent to a central laboratory and were assessed for MRD using flow cytometry and a sequencing methodology.

    Measured: Up to EOT (up to 24 months)

  11. Correlation Between MRD Status and Progression Free Survival (PFS)

    PFS is defined as the time from the date of randomization to the date of first documentation of PD as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurred first, assessed for up to 107 months in this outcome measure.

    Measured: From randomization up to 107 months

  12. Correlation Between MRD Status and Overall Survival (OS)

    OS was measured as the time from the date of randomization to the date of death, assessed for up to 107 months in this outcome measure.

    Measured: From randomization up to 107 months

  13. OS Benefits in a High-Risk Population

    High-risk population included but was not limited to participants carrying deletion (del)17, t(4:14), t(14:16), amplification (ampl) 1q, del13, or del1p. OS was measured as the time from the date of randomization to the date of death.

    Measured: Randomization up to 107 months

  14. PFS Benefits in a High-Risk Population

    High-risk population included but not be limited to participants carrying deletion (del)17, t(4:14), t(14:16), amplification (ampl) 1q, del13, or del1p. PFS was defined as the time from the date of randomization to the date of first documentation of PD, as evaluated by an independent review committee according to IMWG criteria, or death due to any cause (whichever occurs first). PD is defined as ≥25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be >10mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be ≥10%;new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development.

    Measured: Randomization up to 107 months

  15. Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Score

    ECOG performance status assesses a participant's performance status on a 6-point scale ranging from 0=fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead. Lower scores indicate improvement.

    Measured: Baseline up to EOT (up to Month 24)

  16. Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) or Serious Adverse Events (SAEs)

    An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation subject administered a drug. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug. An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital abnormality or birth defect, an important medical event.

    Measured: Up to 107 months

  17. Number of Participants With Markedly Abnormal Clinical Laboratory Values Reported as TEAEs

    Laboratory tests included chemistry, hematology and urinalysis. Abnormal laboratory value was assessed as an AE if the value led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug.

    Measured: Up to 107 months

  18. Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Domain Score

    The EORTC QLQ-C30 is a 30-item questionnaire used to assess the health-related quality of life of cancer patients. GHS/QoL domain is based on questions 29 ("How would you rate your overall health during the past week?") and 30 ("How would you rate your overall quality of life during the past week?") of the EORTC QLQ-C30 where the study participants' self-reported responses to the questions on a 7-point scale (1=very poor to 7=excellent). The raw GHS/QoL domain scores were linearly transformed to a scale ranging 0 (worse outcome) to 100 (best outcome), with higher scores indicating better quality of life. The change from baseline in EORTC QLQ-C30 GHS/QoL domain was evaluated by treatment group.

    Measured: Baseline up to EOT (up to Month 24)

  19. Plasma Concentration of Ixazomib

    Plasma concentrations of the complete hydrolysis product of ixazomib citrate (ixazomib) were measured using a validated Liquid Chromatography-tandem Mass Spectrometry (LC/MS/MS) assay.

    Measured: Day 1 of Cycle 1: 1 hour and 4 hours post-dose; Predose on Days 8 and 15 of Cycle 1, Days 1 and 8 of Cycle 2, Day 1 of Cycles 3 through 10 (each cycle length= 28 days)

  20. Time to Resolution of Peripheral Neuropathy (PN) Events

    Peripheral neuropathy is defined as the TEAE in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as improved if the event improves from the maximum grade. That is, all the grades recorded after the maximum grade is less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.

    Measured: Up to 107 months

  21. Time to Improvement of PN Events

    PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. A PN event is considered as improved if the event improves from the maximum grade. That is, all the grades recorded after the maximum grade is less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.

    Measured: Up to 107 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jul 2014 (estimated)
  2. Study start16 Jul 2014
  3. Primary completion16 Apr 2018
  4. Study completion8 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
656 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02181413
Sponsor's protocol ID
C16019
Other IDs
U1111-1155-8695, 2013-002076-41, C16019CTIL, NL.47795.029.14, 173116, 1036024001, SNCTP000001745
Status last verified
Oct 2024
First submitted
27 Jun 2014
Last updated
19 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Publications

  • Paiva B, Manrique I, Dimopoulos MA, Gay F, Min CK, Zweegman S, Spicka I, Teipel R, Mateos MV, Giuliani N, Cavo M, Hopkins CR, Fu W, Suryanarayan K, Vorog A, Li C, Wang B, Estevam J, Labotka R, Dash AB. MRD dynamics during maintenance for improved prognostication of 1280 patients with myeloma in the TOURMALINE-MM3 and -MM4 trials. Blood. 2023 Feb 9;141(6):579-591. doi: 10.1182/blood.2022016782.

    PubMed 36130300

  • Kaiser M, Beksac M, Gulbrandsen N, Schjesvold F, Hajek R, Moreau P, de Arriba de la Fuente F, Mateos MV, West S, Spencer A, Rajkumar SV, Suryanarayan K, Czorniak M, Li C, Teng Z, Labotka R, Dimopoulos MA. Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma. Ann Hematol. 2020 Aug;99(8):1793-1804. doi: 10.1007/s00277-020-04149-5. Epub 2020 Jul 1.

    PubMed 32613281

  • Schjesvold F, Goldschmidt H, Maisnar V, Spicka I, Abildgaard N, Rowlings P, Cain L, Romanus D, Suryanarayan K, Rajkumar V, Odom D, Gnanasakthy A, Dimopoulos M. Quality of life is maintained with ixazomib maintenance in post-transplant newly diagnosed multiple myeloma: The TOURMALINE-MM3 trial. Eur J Haematol. 2020 May;104(5):443-458. doi: 10.1111/ejh.13379. Epub 2020 Feb 22.

    PubMed 31880006

  • Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, Goldschmidt H, Maisnar V, Moreau P, Min CK, Pluta A, Chng WJ, Kaiser M, Zweegman S, Mateos MV, Spencer A, Iida S, Morgan G, Suryanarayan K, Teng Z, Skacel T, Palumbo A, Dash AB, Gupta N, Labotka R, Rajkumar SV; TOURMALINE-MM3 study group. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019 Jan 19;393(10168):253-264. doi: 10.1016/S0140-6736(18)33003-4. Epub 2018 Dec 10.

    PubMed 30545780

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ixazomib Citrate in people with Multiple Myeloma and Autologous Stem Cell Transplant, run by Takeda at 227 sites in 33 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 227 sites in Germany, Japan, Brazil, Israel, Italy and 28 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: Randomization up to End of treatment (EOT) (24 months); thereafter followed up every 4 weeks (up to 45 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02181413, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2024.

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